OBJECTIVES: To describe sonographic features of the microcystic elongated and fragmented (MELF) pattern of myometrial invasion (MI) using the International Endometrial Tumor Analysis (IETA) criteria; to assess the effect of the MELF pattern on preoperative ultrasound evaluation of MI; and to determine the relationship of the MELF pattern to more advanced stage (≥ IB) and lymph node metastases in women with endometrioid endometrial cancer. METHODS/MATERIALS: We included 850 women with endometrioid endometrial cancer from the prospective IETA 4 study. Ultrasound experts performed all ultrasound examinations, according to the IETA protocol. Reference pathologists assessed the presence or absence of the MELF pattern. Sonographic features and accuracy of ultrasound assessment of MI were compared in cases with the presence and the absence of the MELF pattern. The MELF pattern was correlated to more advanced stage (≥IB) and lymph node metastases. RESULTS: The MELF pattern was present in 197 (23.2%) women. On preoperative ultrasound imaging the endometrium was thicker (p = 0.031), more richly vascularized (p = 0.003) with the multiple multifocal vessel pattern (p < 0.001) and the assessment of adenomyosis was more often uncertain (p < 0.001). The presence or the absence of the MELF pattern did not affect the accuracy of the assessment of MI. The MELF pattern was associated with deep myometrial invasion (≥ 50%) (p < 0.001), cervical stromal invasion (p = 0.037), more advanced stage (≥ IB) (p < 0.001) and lymph node metastases (p = 0.011). CONCLUSIONS: Tumors with the MELF pattern were slightly larger, more richly vascularized with multiple multifocal vessels and assessment of adenomyosis was more uncertain on ultrasound imaging. The MELF pattern did not increase the risk of underestimating MI in preoperative ultrasound staging. Tumors with the MELF pattern were more than twice as likely to have more advanced stage (≥ IB) and lymph node metastases.

• Klíčová slova
• MELF, diagnostic imaging, endometrial neoplasms, neoplasm staging, ultrasonography,
• MeSH
• histiocyty patologie   MeSH
• hysterektomie MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfadenektomie MeSH
• lymfatické uzliny diagnostické zobrazování   patologie   chirurgie   MeSH
• myometrium diagnostické zobrazování   patologie   chirurgie   MeSH
• nádory endometria diagnostické zobrazování   patologie   chirurgie   MeSH
• následné studie MeSH
• prognóza MeSH
• prospektivní studie MeSH
• senioři MeSH
• ultrasonografie metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

OBJECTIVES: The aim is to estimate agreement between two-dimensional transvaginal ultrasound (2D-TVS) and three-dimensional volume contrast imaging (3D-VCI) in diagnosing deep myometrial invasion (MI) and cervical stromal involvement (CSI) of endometrial cancer and to compare the two methods regarding inter-rater reliability and diagnostic accuracy. METHODS: Fifteen ultrasound experts assessed off-line de-identified 3D-VCI volumes and 2D-TVU video clips from 58 patients with biopsy-confirmed endometrial cancer regarding the presence of deep (≥50%) MI and CSI. Video clips and 3D volumes were assessed independently. Interrater reliability was measured using kappa statistics. Histological diagnosis after hysterectomy served as gold standard. Accuracy measurements were correlated to rater experience using Spearman's rank correlation coefficient (ρ). RESULTS: Agreement between 2D-TVU and 3D-VCI for diagnosing MI was median 76% (range 64-93%) and for CSI median 88% (range 79-97%). Interrater reliability was better for 2D-TVU than for 3D-VCI (Fleiss' kappa 0.41 vs. 0.31 for MI and 0.55 vs. 0.45 for CSI). Median accuracy for diagnosing deep MI was 76% (range 59-84%) with 2D-TVU and 69% (range 52-83%) for 3D-VCI; the corresponding figures for CSI were 88% (range 81-93%) and 86% (range 72-95%). Accuracy was significantly correlated to how many cases the raters assessed annually. CONCLUSIONS: Off-line assessment of MI and CSI in women with endometrial cancer using 3D-VCI has lower interrater reliability and lower accuracy than 2D-TVU video clip assessment. Since accuracy was correlated to the number of cases assessed annually it is advised to centralize these examinations to high-volume centres.

• Klíčová slova
• Diagnostic imaging, Endometrial neoplasms, Neoplasm staging, Reproducibility of results, Three-dimensional imaging, Ultrasonography,
• MeSH
• dospělí MeSH
• invazivní růst nádoru MeSH
• kontrastní látky MeSH
• lidé středního věku MeSH
• lidé MeSH
• myometrium diagnostické zobrazování   patologie   MeSH
• nádory endometria diagnostické zobrazování   patologie   chirurgie   MeSH
• odchylka pozorovatele MeSH
• reprodukovatelnost výsledků MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů metody   MeSH
• ultrasonografie metody   MeSH
• zobrazování trojrozměrné * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• kontrastní látky MeSH

OBJECTIVE: To investigate differences and similarities in the clinical approach of young clinicians managing women with endometrial cancer (EC) conservatively. METHODS: A web-based survey was carried out. A platform of the European Network of Young Gynaecological Oncologists (ENYGO) database was used. A 38-item multiple-choice questionnaire was used to evaluate current practice in fertility-sparing management of EC. The survey covered investigations, treatment options, follow-up and management of recurrence and future family planning. Descriptive statistics were used. RESULTS: Overall, 116 out of 650 (17.84%) ENYGO members responded to the survey. In 92 (79.3%) centres, the caseload of early stage EC treated conservatively was less than 10 per year. One hundred and seven responders (93.8%) believe that treatment with progestins could be offered in grade 1 EC without myometrial invasion, but a minority would recommend it even for grade 2 tumours with no myometrial invasion or grade 1 with superficial invasion. The diagnostic tool for establishing grade of tumour was hysteroscopy with dilatation and curettage in 64 (55%) centres. Medroxyprogesterone acetate represents the most commonly prescribed progestogen (55, 47.4%). In 78 (67.2%) centres, a repeat endometrial biopsy was offered after 3 months of treatment commencement. Recurrences are treated mostly with hysterectomy (81, 69.9%) with only a small number of responders recommending to repeat progestin treatment. Lynch syndrome is a contraindication for conservative management in half of the responders (57, 49.1%). Most clinicians agree that patients should be referred promptly for assisted reproductive techniques once complete response has been achieved (68, 58.6%). CONCLUSIONS: Our study shows that conservative management is increasingly offered to women affected by early stage EC wishing to preserve their fertility. Further studies and joint registries are required to evaluate safety and effectiveness of this approach in this probably growing number of patients.

• Klíčová slova
• Assisted reproduction, Conservative management, Endometrial cancer, Pregnancies, Progestins,
• MeSH
• asistovaná reprodukce MeSH
• dilatace a kyretáž MeSH
• dospělí MeSH
• endometrium patologie   MeSH
• hormonální protinádorové látky terapeutické užití   MeSH
• hysteroskopie MeSH
• konzervativní terapie metody   MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   terapie   MeSH
• medroxyprogesteronacetát terapeutické užití   MeSH
• myometrium patologie   MeSH
• nádory endometria farmakoterapie   patologie   MeSH
• progestiny terapeutické užití   MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• výsledek terapie MeSH
• zachování plodnosti MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• hormonální protinádorové látky MeSH
• medroxyprogesteronacetát MeSH
• progestiny MeSH

Uterine leiomyosarcomas (uLMS) are rare, aggressive malignancies for which limited treatment options are available. To gain novel molecular insights into uLMS and identify potential novel therapeutic targets, we characterized 84 uLMS samples for genome-wide somatic copy number alterations, mutations, gene fusions and gene expression and performed a data integration analysis. We found that alterations affecting TP53, RB1, PTEN, MED12, YWHAE and VIPR2 were present in the majority of uLMS. Pathway analyses additionally revealed that the PI3K/AKT/mTOR, estrogen-mediated S-phase entry and DNA damage response signaling pathways, for which inhibitors have already been developed and approved, frequently harbored genetic changes. Furthermore, a significant proportion of uLMS was characterized by amplifications and overexpression of known oncogenes (CCNE1, TDO2), as well as deletions and reduced expression of tumor suppressor genes (PTEN, PRDM16). Overall, it emerged that the most frequently affected gene in our uLMS samples was VIPR2 (96%). Interestingly, VIPR2 deletion also correlated with unfavorable survival in uLMS patients (multivariate analysis; HR = 4.5, CI = 1.4-14.3, p = 1.2E-02), while VIPR2 protein expression was reduced in uLMS vs. normal myometrium. Moreover, stimulation of VIPR2 with its natural agonist VIP decreased SK-UT-1 uLMS cell proliferation in a dose-dependent manner. These data suggest that VIPR2, which is a negative regulator of smooth muscle cell proliferation, might be a novel tumor suppressor gene in uLMS. Our work further highlights the importance of integrative molecular analyses, through which we were able to uncover the genes and pathways most frequently affected by somatic alterations in uLMS.

• Klíčová slova
• RNA sequencing, copy number alteration, data integration, molecular profiling, uterine leiomyosarcoma,
• MeSH
• dospělí MeSH
• genomika metody   MeSH
• Kaplanův-Meierův odhad MeSH
• karcinogeneze genetika   MeSH
• leiomyosarkom genetika   mortalita   patologie   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myometrium patologie   MeSH
• nádory dělohy genetika   mortalita   patologie   terapie   MeSH
• onkogeny genetika   MeSH
• proliferace buněk genetika   MeSH
• receptory vazoaktivního intestinálního peptidu typu II genetika   MeSH
• regulace genové exprese u nádorů genetika   MeSH
• sekvenční analýza RNA metody   MeSH
• sekvenování celého genomu metody   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• signální transdukce genetika   MeSH
• tumor supresorové geny MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• receptory vazoaktivního intestinálního peptidu typu II MeSH
• VIPR2 protein, human MeSH Prohlížeč

The aim of this study was to assess the diagnostic accuracy of subjective ultrasound evaluation of myometrial invasion of endometrial cancer and to compare its accuracy to objective methods. All consecutive patients with histologically proven endometrial cancer, who underwent ultrasound evaluation followed by surgical staging between January 2009 and December 2011, were prospectively enrolled. Myometrial invasion was evaluated by subjective assessment using ultrasound (<50% or ≥50%) and calculated as deepest invasion/normal myometrium ratio (Gordon's ratio) and as tumor/uterine anteroposterior diameter ratio (Karlsson's ratio). Histological assessment from hysterectomy was considered the gold standard. Altogether 210 patients were prospectively included. Subjective assessment and two objective ratios were found to be statistically significant predictors of the myometrial invasion (AUC = 0.65, p value < 0.001). Subjective assessment was confirmed as the most reliable method to assess myometrial invasion (79.3% sensitivity, 73.2% specificity, and 75.7% overall accuracy). Deepest invasion/normal myometrium (Gordon's) ratio (cut-off 0.5) reached 69.6% sensitivity, 65.9% specificity, and 67.3% overall accuracy. Tumor/uterine anteroposterior diameter (Karlsson's) ratio with the same cut-off reached 56.3% sensitivity, 76.4% specificity, and 68.1% overall accuracy. The subjective ultrasound evaluation of myometrial invasion performed better than objective methods in nearly all measures but showed statistically significantly better outcomes only in case of sensitivity.

• MeSH
• invazivní růst nádoru diagnóza   diagnostické zobrazování   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myometrium diagnostické zobrazování   patologie   chirurgie   MeSH
• nádory endometria diagnóza   diagnostické zobrazování   patologie   chirurgie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ultrasonografie * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

AIM: An optimal surgical staging in the group of patients with the high-risk type of endometrial cancer is often limited by age and serious internal comorbidities. Therefore, in this study we focused on human epididymis protein 4 and its contribution to the preoperative differentiation of prognostically distinct groups of patients and to individualized surgical treatment as compared with cancer antigen (CA) 125 and imaging methods. MATERIAL AND METHODS: The study included 115 patients with endometrioid adenocarcinoma diagnosed through endometrial biopsy. Before the final operation, blood sampling was performed for the determination of human epididymis protein 4 (HE4) and CA125 levels. Serum levels of both biomarkers were analyzed in relation to individual prognostic factors (stage of disease, depth of myometrial invasion, tumor grade, risk type of disease). RESULTS: In the case of HE4, we demonstrated a statistically significant difference (P < 0.001) between patients with low and high risk of the disease. In our model, achieving the maximum sum of sensitivity and specificity, HE4 shows a sensitivity of 72.4% and a specificity of 75.4% for the cut-off 76.5 pmol/L and is a better predictor in distinguishing the high-risk patients than CA125 (area under the curve 0.77 for HE vs 0.71 for CA125). CONCLUSION: HE4 is a marker that could complement the findings of imaging techniques and that may be useful in decision-making on how to individualize surgical staging. The possibility of its introduction as an independent marker in routine practice remains, at the moment however, limited. The optimal cut-off for HE4 has not been established yet and further studies are needed.

• Klíčová slova
• endometrial cancer, human epididymis protein 4, risk status of disease, surgical staging,
• MeSH
• antigen CA-125 krev   MeSH
• endometroidní karcinom krev   patologie   MeSH
• lidé MeSH
• membránové proteiny krev   MeSH
• myometrium patologie   MeSH
• nádorové biomarkery krev   MeSH
• nádory endometria krev   patologie   MeSH
• protein WFDC2 MeSH
• proteiny metabolismus   MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigen CA-125 MeSH
• membránové proteiny MeSH
• MUC16 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protein WFDC2 MeSH
• proteiny MeSH
• WFDC2 protein, human MeSH Prohlížeč

OBJECTIVES: To identify major factors in the under- and overestimation of cervical and myometrial invasion by endometrial cancer at preoperative staging by ultrasound. METHODS: This prospective study involved all patients with histologically confirmed endometrial cancer referred consecutively for surgical staging between January 2009 and December 2011. All patients underwent transvaginal ultrasound examination, obtaining metric and perfusion data, and the results were compared with final histology: myometrial invasion was defined at histology in the final pathology report as being either < or ≥ 50%, while cervical stromal invasion was reported as being either present or absent, and sonographic over-/underestimation was determined relative to these. RESULTS: Enrolled prospectively into the study were 210 patients. The proportion of cases with sonographic underestimation, relative to final histology, of myometrial invasion (i.e. false-negative estimation of no or superficial invasion < 50%) and of cervical invasion (i.e. false-negative finding of absence of stromal invasion) was comparable: 8.6% (n = 18) and 10.5% (n = 22), respectively. Myometrial invasion was overestimated by ultrasound (i.e. false-positive estimation of deep invasion ≥ 50%) in 15.7% (n = 33) of cases, and cervical invasion was overestimated (i.e. false-positive finding of presence of stromal invasion) in 4.8% (n = 10) of cases. These outcomes correspond to positive and negative predictive values of 67.6% (95% CI, 57.7-76.6) and 83.3% (95% CI, 74.9-89.8), respectively, for the subjective assessment of myometrial invasion, and 60.0% (95% CI, 38.2-79.2) and 88.1% (95% CI, 82.5-92.4), respectively, for that of cervical stromal invasion. The staging error in subjective assessment was not related to body mass index (BMI), to the position of the uterus in the pelvis or to image quality. Cervical and myometrial invasion were more often underestimated in well-differentiated endometrial cancers that were smaller in size, with thick minimum tumor-free myometrium and lower perfusion, and more often overestimated in moderately and poorly differentiated cancers that were larger in size, with thin minimum tumor-free myometrium and richer perfusion. CONCLUSION: The accuracy of subjective assessment of myometrial and cervical invasion by ultrasound was significantly influenced by tumor size, density of tumor vascularization, tumor vessel architecture and histological grading, while it was not significantly affected by BMI, uterine position and image quality.

• Klíčová slova
• FIGO staging, cervical stromal invasion, endometrial cancer, myometrial invasion, transvaginal sonography, ultrasound,
• MeSH
• cervix uteri diagnostické zobrazování   patologie   MeSH
• index tělesné hmotnosti MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• myometrium diagnostické zobrazování   patologie   MeSH
• nádory endometria diagnostické zobrazování   patologie   MeSH
• pohyb buněk MeSH
• předoperační péče metody   MeSH
• prospektivní studie MeSH
• reprodukovatelnost výsledků MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• ultrasonografie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: The aim of our retrospective study was to correlate the intraoperative frozen section (FS) and permanent section (PS) diagnosis among patients with early-stage endometrial cancer (FIGO Stage I). METHODS: Retrospective analysis of clinical data. A set of 63 women were operated by the technique of laparoscopic assisted vaginal hysterectomy with bilateral salpingo-oophorectomy (LAVH with BSO). All probands had intraoperative FS biopsy performed with grading and myometrial invasion assessment. These data were then compared with PS diagnosis. Statistical evaluation was used to detect diagnostic accuracy of FS (sensitivity, specificity and positive vs negative predictive value, and accuracy rate). RESULTS: The average age was 61 years, BMI 32.4 kg/m2 and operation time including lymphadenectomy (LAE) was 108.7 minutes. Sensitivity of FS was 77.8%, specificity 98.1%, positive predictive value (PPV) 87.5%, negative predictive value (NPV) 96.4% and accuracy rate 95.2%. Suboptimal surgical management due to underevaluation of FS biopsy compared to PS diagnosis occurred in 2 patients (3.2%). CONCLUSION: Combination of LAVH with BSO and use of intraoperative FS enables the surgeon to individualize surgical treatment for every patient to the extent of either performing complete operation together with LAE or not.

• MeSH
• adenokarcinom patologie   chirurgie   MeSH
• biopsie * MeSH
• dospělí MeSH
• hysterektomie vaginální MeSH
• laparoskopie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfadenektomie MeSH
• myometrium patologie   MeSH
• nádory endometria patologie   chirurgie   MeSH
• ovarektomie MeSH
• prediktivní hodnota testů MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• vejcovody chirurgie   MeSH
• zmrazené řezy * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: To compare the accuracy of transvaginal sonography and magnetic rezonance imaging (MRI) in determining the depth of myometrial invasion in proven cases of endometrial cancer. DESIGN: A prospective study. SETTING: Department of Obstetrics and Gynecology, Department of Medical Genetics and Fetal Medicine, Department of Radiology, University Hospital, Olomouc. METHODS: Fifty five patients diagnosed as having FIGO stage I endometrial carcinoma were evaluated preoperatively by transvaginal ultrasound; 44 cases of the same group were also evaluated by magnetic resonance imaging (MRI). The degree of invasion evaluated by transvaginal sonography and by MRI was compared to the pathological specimens. RESULTS: Transvaginal sonography was successful in evaluating myometrial invasion in 44 of 55 cases (accuracy 80%, sensitivity 80%, specificity 88%, positive predictive value 77%, negative predictive value 87%). Evaluation with MRI was accurate in 37 of 44 cases (accuracy 84%, sensitivity 84%, specificity 91%, positive predictive value 81%, negative predictive value 91%). CONCLUSION: Although MRI is superior to transvaginal sonography in evaluating myometrial invasion, it is expensive and time consuming, and would not be suitable as a screening test for depth of invasion. On the other hand, transvaginal sonography is relatively low-cost technique, which can be easily performed and repeated. However, it requires more operator experience than MRI in order to achieve high accuracy.

• MeSH
• invazivní růst nádoru MeSH
• karcinom diagnóza   diagnostické zobrazování   patologie   chirurgie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• myometrium diagnostické zobrazování   patologie   MeSH
• nádory endometria diagnóza   diagnostické zobrazování   patologie   chirurgie   MeSH
• prediktivní hodnota testů MeSH
• senzitivita a specificita MeSH
• ultrasonografie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

An unusual low-grade metaplastic carcinoma (müllerian carcinosarcoma) of the uterine corpus occurring in a 45-year-old woman is presented. The tumor was polypoid and showed an initial invasion into the myometrium. The epithelial component was composed of low-grade endometrioid glands that focally showed an unusual oxyphilic change of the cytoplasm. These cells contained only a small amount of mitochondria detected with antimitochondrial antibody. The stromal component contained small round cells of bland appearance and appeared to arise from epithelial cells through a metaplastic process, as a gradual transition between epithelial and stromal cells was often seen. An invasive marginal zone of the tumor showed endometrioid adenocarcinoma pattern without any stromal component. The proliferative activity generally was low. Interestingly, it was clearly accentuated in the epithelial component especially in the peripheral invasive areas, whereas it was very low in the stromal component. The course of disease was indolent. Low-grade müllerian carcinosarcoma is to be distinguished from other biphasic müllerian tumors.

• MeSH
• endometroidní karcinom patologie   MeSH
• karcinosarkom patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metaplazie patologie   MeSH
• myometrium patologie   MeSH
• nádory dělohy patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH